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Therefore, searching for effective agents for the treatment of radiation colitis is urgently needed. Herein, it is found that the essential element selenium (Se) is protective against radiation colitis through inhibiting X\u2010ray\u2010induced apoptosis, cell cycle arrest, and inflammation with the involvement of balancing the generation of reactive oxygen species after the irradiation. Mechanistically, Se, especially for selenium nanoparticles (SeNPs), induced selenoprotein expression and then functioned to effectively restrain DNA damage response, which reduced X\u2010ray\u2010induced intestinal injury. Additionally, SeNPs treatment also restrained the cyclic GMP\u2010AMP synthas (cGAS)\u2010 stimulator of interferon genes (STING)\u2010TBK1\u2010IRF3 signaling pathway cascade, thereby blocking the transcription of inflammatory cytokine gene, IL\u20106 and TNF\u2010\u03b1, and thus alleviating inflammation. Moreover, inducing selenoprotein expression, such as GPX4, with SeNPs in vivo can regulate intestinal microenvironment immunity and gut microbiota to attenuate radiation\u2010induced colitis by inhibiting oxidative stress and maintaining microenvironment immunity homeostasis. Together, these results unravel a previously unidentified modulation role that SeNPs restrained radiation colitis with the involvement of inducing selenoprotein expression but suppressing cGAS\u2010STING\u2010TBK1\u2010IRF3 cascade.<\/jats:p>","DOI":"10.1002\/advs.202403918","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T12:40:14Z","timestamp":1727700014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Selenium Attenuates Radiation Colitis by Regulating cGAS\u2010STING Signaling"],"prefix":"10.1002","volume":"11","author":[{"given":"Qian","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology of Puning People's Hospital Department of Chemistry of Jinan University State Key Laboratory of Bioactive Molecules and Druggalibility Assessment MOE Key Laboratory of Tumor Molecular Biology Jinan University  Guangdong 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